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Effects of reinforcement schedule on facilitation of operant extinction by chlordiazepoxide.

Learning and memory are central topics in behavioral neuroscience, and inbred mice strains are widely investigated. However, operant conditioning techniques are not as extensively used in this field as they should be, given the effectiveness of the methodology of the experimental analysis of behavior. In the present study, male C57B1/6 mice, widely used as background for transgenic studies, were trained to lever press on discrete-trial fixed-ratio 5 or fixed-interval (11 s or 31 s) schedules of food reinforcement and then exposed to 15 extinction sessions following vehicle or chlordiazepoxide injections (15 mg/kg i.p., administered either prior to all extinction sessions, or prior to the final 10 extinction sessions). Extinction of operant behavior was facilitated by drug administration following training on either schedule, but this facilitation only occurred once a number of extinction sessions had taken place. The extinction process proceeded more rapidly following fixed-interval training. Resistance to extinction was equally high following training with either schedule type, and was reduced by drug administration in both cases. These phenomena were evident in individual cumulative records and in analyses of group data. Results are interpreted in terms of phenomena of operant extinction identified in Skinner's (1938) Behavior of Organisms, and by behavioral momentum theory. These procedures could be used to extend the contribution of operant conditioning to contemporary behavioral neuroscience.

Animals↗

Modeling the survival of Salmonella spp. in chorizos.

The survival of Salmonella spp. in chorizos has been studied under the effect of storage conditions; namely temperature (T=6, 25, 30 degrees C), air inflow velocity (F=0, 28.4 m/min), and initial water activity (a(w0)=0.85, 0.90, 0.93, 0.95, 0.97). The pH was held at 5.0. A total of 20 survival curves were experimentally obtained at various combinations of operating conditions. The chorizos were stored under four conditions: in the refrigerator (Ref: T=6 degrees C, F=0 m/min), at room temperature (RT: T=25 degrees C, F=0 m/min), in the hood (Hd: T=25 degrees C, F=28.4 m/min), and in the incubator (Inc: T=30 degrees C, F=0 m/min). Semi-logarithmic plots of counts vs. time revealed nonlinear trends for all the survival curves, indicating that the first-order kinetics model (exponential distribution function) was not suitable. The Weibull cumulative distribution function, for which the exponential function is only a special case, was selected and used to model the survival curves. The Weibull model was fitted to the 20 curves and the model parameters (alpha and beta) were determined. The fitted survival curves agreed with the experimental data with R(2)=0.951, 0.969, 0.908, and 0.871 for the Ref, RT, Hd, and Inc curves, respectively. Regression models relating alpha and beta to T, F, and a(w0) resulted in R(2) values of 0.975 for alpha and 0.988 for beta. The alpha and beta models can be used to generate a survival curve for Salmonella in chorizos for a given set of operating conditions. Additionally, alpha and beta can be used to determine the times needed to reduce the count by 1 or 2 logs t(1D) and t(2D). It is concluded that the Weibull cumulative distribution function offers a powerful model for describing microbial survival data. A comparison with the pathogen modeling program (PMP) revealed that the survival kinetics of Salmonella spp. in chorizos could not be adequately predicted using PMP which underestimated the t(1D) and t(2D). The mean of the Weibull probability density function correlated strongly with t(1D) and t(2D), and can serve as an alternative to the D-values normally used with first-order kinetic models. Parametric studies were conducted and sensitivity of survival to operating conditions was evaluated and discussed in the paper. The models derived herein provide a means for the development of a reliable risk assessment system for controlling Salmonella spp. in chorizos.

Animals↗

Total intravenous anaesthesia with ketamine-midazolam versus halothane-nitrous oxide-oxygen anaesthesia for prolonged abdominal surgery.

BACKGROUND AND OBJECTIVE: Total intravenous anaesthesia (TIVA) with ketamine-midazolam (KM) can be used for prolonged abdominal surgery. We compared this technique with halothane-nitrous oxide-oxygen anaesthesia using haemodynamic and endocrine stress responses as primary outcomes and adequacy of operating conditions and recovery profile as secondary outcomes. METHODS: Fifty adult patients undergoing radical cystectomy and bladder substitution were randomly assigned to receive either TIVA with KM (n = 25) or halothane, nitrous oxide and oxygen anaesthesia (n = 25). Invasive haemodynamic and oxygenation variables were monitored along with plasma cortisol and growth hormone concentrations. Operative conditions and recovery profiles were registered. RESULTS: Cardiac index and vascular resistance remained stable during and after surgery. Cortisol concentrations doubled during surgery and remained elevated in the recovery period. Growth hormone increased after induction, peaked during surgery and decreased during recovery. Neither the haemodynamic variables nor the plasma hormone concentrations differed significantly between the two groups. Intestinal loops were collapsed in the KM groups providing better operative conditions and a reduced need for postoperative analgesics. CONCLUSIONS: The stress responses during KM anaesthesia for prolonged abdominal surgery were comparable to those during halothane-nitrous oxide-oxygen anaesthesia. However, KM anaesthesia provided better surgical conditions and better recovery.

Adult↗

Stability in a denitrifying fluidized bed reactor.

This study evaluates changes in the microbial community structure and function of a pilot-scale denitrifying fluidized bed reactor during periods of constant operating conditions and periods of perturbation. The perturbations consisted of a shutdown period without feed, two disturbances in which biofilms were mechanically sheared from carrier particles, and a twofold step increase in feed nitrate concentration. In the absence of perturbations, nitrate removal was stable and consistently greater than 99%. The structure and dynamics of the microbial community were studied using cloning and sequencing techniques and terminal restriction fragment length polymorphism (T-RFLP) of the SSU rRNA gene. Under unperturbed operating conditions, stable function was accompanied by high constancy and low variability of community structure with the majority of terminal restriction fragments (T-RFs) appearing throughout operation at consistent relative abundances. Several of the consistently present T-RFs correlated with clone sequences closely related to Acidovorax (98% similarity), Dechloromonas (99% similarity), and Zoogloea (98% similarity), genera recently identified by molecular analyses of similar systems. Significant changes in community structure and function were not observed after the shutdown period. In contrast, following the increase in loading rate and the mechanical disturbances, new T-RFs appeared. After both mechanical disturbances, function and community structure recovered. However, function was much more resilient than community structure. The similarity of response to the mechanical disturbances despite differences in community structure and operating conditions suggests that flexible community structure and potentially the activity of minor members under nonperturbation conditions promotes system recovery.

Biodegradation, Environmental↗

A multiple chemical equilibria approach to modeling and interpreting the separation of amino acid enantiomers by chiral ligand-exchange chromatography.

A model of chiral ligand-exchange chromatography (CLEC) is presented that combines the non-ideal equilibrium-dispersion equation for solute transport with equations describing all chemical equilibria within the column. The model connects elution band profiles to the time and space resolved formation of diastereomeric complexes in both the mobile and stationary phases, thereby providing insights into the overall separation mechanism. The stoichiometries and formation constants for all equilibrium complexes formed in the mobile phase are taken from standard thermodynamic databases and independent potentiometric titration experiments. Formation constants for complexes formed with the stationary phase ligand are determined from potentiometric titration data for a water-soluble analogue of the ligand. Together this set of pure thermodynamic parameters can be used to calculate the equilibrium composition of the system at any operating condition. The model includes a temperature-dependent pure-component parameter, determined by regression to a single elution band for the pure component, that corrects for subtle effects associated with immobilizing the ligand (i.e., the chiral selector) onto the stationary phase. Model performance is assessed through comparison with chromatograms for two hydrophobic amino acid racemates loaded on the Nucleosil Chiral-1 CLEC column. The model is also applied to a restricted optimization of column operating conditions to assess its predictive power. In both cases, model predictions compare well with experiment while also providing a molecular understanding of the separation process and its dependence on column operating conditions.

Amino Acids↗

Behavioral observations and operant procedures using microwaves as a heat source for young chicks.

Four trials, using operant conditioning procedures, were conducted to study the response of chicks, housed at 16 C, to microwave or infrared heat. Microwave power density was 26 mW/cm2 in Trial 1, 13 mW/cm2 in Trial 2, and 10 mW/cm2 in Trials 3 and 4. Chicks voluntarily demanded between 28 and 63% as much heat (min heat/hr) from microwave source as from infrared source at all power densities. There was no correlation, however, between the ratio of heat demanded and the power density used. There were no significant differences in growth between infrared- or microwave-heated chicks. It is evident from these studies that 8-day-old broiler chicks are capable of associating the performance of a task with a thermal reward provided by the microwaves. They are also able to utilize these microwaves through operant conditioning without any visible detrimental effect to their health or behavior.

Animals↗

Biofeedback effect on electromyography responses in patients with spinal cord injury.

OBJECTIVE: To determine if electromyography (EMG) biofeedback procedures using an operant conditioning paradigm could significantly increase voluntary EMG responses from the triceps muscles of long term cervical spinal cord injured individuals. DESIGN: Intervention study with before-after trial measurement with each subject as its own control. SETTING: University outpatient clinic. PARTICIPANTS: One hundred individuals with cervical spinal cord injuries C6 or higher that were greater than 1-year duration, and who had less than normal strength and recordable EMG activity from the triceps, and who had reached a plateau in return of function. The first 100 individuals meeting this criteria who presented sequentially for EMG testing and biofeedback were included. No subjects were deleted from the sample. INTERVENTION: Muscle strength and surface EMG recording during attempts at elbow extension were obtained. The EMG pretest data were derived from the highest average recorded voluntary EMG response from the triceps during elbow extension. One 45-minute treatment session of EMG biofeedback for the triceps in an operant conditioning paradigm was provided for each of the 100 subjects. Seventy-five subjects received an average of 3 additional biofeedback treatment sessions. The posttest EMG data were derived from EMG measurements of the triceps during attempts at elbow extension from the 45-minute biofeedback treatment session and from the last additional biofeedback treatment session in a similar manner to the pretest procedures. MAIN OUTCOME MEASURES: A significant increase in EMG activity occurred from the triceps (p < or = .001) after one biofeedback treatment session and further significant increases in EMG activity occurred after additional biofeedback treatment sessions (p < or = .001). Initial muscle strength and initial EMG levels were not determining factors for response to the biofeedback. CONCLUSIONS: The results suggest the efficacy of biofeedback for increasing voluntary EMG responses in long term spinal cord injury patients.

Adolescent↗

Extinction requires new RNA and protein synthesis and the soma of the cell right pedal dorsal 1 in Lymnaea stagnalis.

Lymnaea stagnalis were operantly conditioned to not perform aerial respiratory behavior. This learned response was subsequently extinguished. Here, we show that spaced extinction training is more effective than massed extinction training, in addition to the occurrence of spontaneous recovery. We also find evidence of a critical period within the first hour after extinction training in which new RNA and protein synthesis must occur for a memory of extinction training to be established. The memory for extinction training can also be extended using cooling and by preventing aerial respiration from occurring after extinction training. In addition, we demonstrate that memory formation of extinction training requires the soma of the cell right pedal dorsal 1, a cell that we have previously shown to be necessary for long-term memory consolidation and reconsolidation. This finding implies that the events that lead to the formation of extinction memory occur in the same cell that is responsible for long-term memory of operant conditioning. All of these data are consistent with the hypothesis that, during extinction, a new associative memory is being formed and that this new memory covers up, but does not abolish, the "old" memory.

Animals↗

Endosulfan induces small but significant changes in the levels of noradrenaline, dopamine and serotonin in the developing rat brain and deficits in the operant learning performance.

The organochlorine insecticide, endosulfan was administered (6 mg/kg body weight) to Wistar rat pups of both sexes by gastric intubation daily from post-natal days 2-25. Its effect on levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) was assayed in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), brainstem (BS) and cerebellum (CB) on days 10 and 25 using high-performance liquid chromatography (HPLC). The activity of acetylcholinesterase (AChE) was also estimated in the same regions of the brain. Performance in operant conditioning for solid food reward was assessed in 25-day-old rats. NA levels were increased in OB (12%, P < 0.01) and BS (10%, P < 0.05) at 10 days of age and in HI (20%, P < 0.01) and CB (12%, P < 0.05) at 25 days of age. DA level was decreased in HI at both 10 (42%, P < 0.001) and 25 (45%, P < 0.001) days. Serotonin levels were increased in OB (12%, P < 0.05), HI (41%, P < 0.001), VC (30%, P < 0.01) and BS (15%, P < 0.01) at 10 days of age but at 25 days, levels were decreased in BS (20%, P < 0.05) and CB (31%, P < 0.01). The activity of AChE was not different from the control groups in any of the regions studied. These data suggest that monoaminergic systems in the developing rat brain respond to endosulfan by undergoing something like a 'reorganization'. However, such changes do not ameliorate certain functional losses following the exposure to endosulfan as operant conditioning revealed deficits in acquisition as well as retention of memory.

Acetylcholinesterase↗

Impaired acquisition and operant responding after neonatal dopamine depletion in rats.

The effect of neonatal dopamine depletion in rats was examined using operant conditioning. Rat pups were given 6-hydroxydopamine (6-OHDA) or sham lesions at 3 days of age. When tested as adults, 6-OHDA treated subjects were impaired in the acquisition of lever pressing for reward and displayed stereotyped sniffing patterns not observed in the control subjects. In addition, significantly lower rates of responding were measured for the lesion group during continuous reinforcement (CRF), dilution of reinforcer efficacy, and with progressively increasing fixed ratio requirements. Alpha-methyl-p-tyrosine (AMPT), given before one CRF session, attenuated responding in over half the lesion animals and in none of the controls. Dopamine content in caudate nucleus was found to significantly correlate with number of trials to acquisition and rates of responding following AMPT in the lesion group, but not in the control group. Overall, the results of this experiment showed that neonatal dopamine depletion does not lead to severe motor impairment or the inability to learn, but does disrupt the normal patterns of behavior associated with operant conditioning.

Animals↗

Hypertension and appraisal of physical and psychological stressors.

OBJECTIVE: In the operant conditioning of hypertension hypothesis, it is assumed that the frequently found diminished sensitivity to painful stimuli in hypertensives can be generalized to sensitivity to other stressors, including psychological stressors. The validity of this assumption is examined in the present study. METHODS: Unmedicated hypertensives (42) and normotensive controls (21) of both sexes were exposed to a physical stressor (electric current) and psychological active coping (mental arithmetic, free speech) and passive coping (unpleasant films) tasks, while indices of prestressor anxiety and task appraisal were measured. RESULTS: Hypertensive women, but not men, showed diminished pain sensitivity, together with lower prestressor anxiety and a tendency to lower negative appraisal of the tasks, compared to their normotensive counterparts. In addition, positive correlations were obtained between pain sensitivity and negative appraisal of psychological stressors involving interpersonal threat (speech) and passive coping (films). CONCLUSION: Preliminary support has been obtained for extrapolation of diminished pain appraisal to appraisal of some psychological stressors (although for a part only in women); an important assumption in the operant conditioning hypothesis of hypertension.

Adaptation, Psychological↗

Volatilization of chemicals from drinking water to indoor air: role of the kitchen sink.

Contaminated tap water is one source of potentially hazardous air pollutants in residential indoor air. Contaminants have been observed to volatilize from household tap water sources, including showers, wash basins, bath-tubs, washing machines, dishwashers, and toilets. A background search of these sources led to the conclusion that more attention should be given to wash basins and tubs, the numerous operating conditions of which yield a significant range of chemical stripping efficiencies. In response, nine laboratory experiments were completed to determine chemical stripping efficiencies and mass transfer coefficients for a kitchen wash basin. Chemical stripping efficiencies ranged from 1.1% to 4.9% for acetone, 13% to 26% for toluene, and 18% to 48% for cyclohexane. The product of overall mass transfer coefficient and interfacial area (KLA) ranged from 0.06 L/min to 0.24 L/min for acetone, 0.7 L/min to 1.9 L/min for toluene, and 0.9 L/min to 3.5 L/min for cyclohexane. Results clearly indicate that chemical properties (e.g., Henry's law coefficient) and system operating conditions (e.g., liquid flow rate and nozzle type) have a significant effect on contaminant stripping efficiency. Furthermore, significant gasphase resistance can occur, even for relatively volatile contaminants, during some operating conditions. The latter observation has important implications with respect to conventional protocols used to extrapolate radon data to other volatile contaminants in drinking water.

Air Pollution, Indoor↗

Genetic programming assisted stochastic optimization strategies for optimization of glucose to gluconic acid fermentation.

This article presents two hybrid strategies for the modeling and optimization of the glucose to gluconic acid batch bioprocess. In the hybrid approaches, first a novel artificial intelligence formalism, namely, genetic programming (GP), is used to develop a process model solely from the historic process input-output data. In the next step, the input space of the GP-based model, representing process operating conditions, is optimized using two stochastic optimization (SO) formalisms, viz., genetic algorithms (GAs) and simultaneous perturbation stochastic approximation (SPSA). These SO formalisms possess certain unique advantages over the commonly used gradient-based optimization techniques. The principal advantage of the GP-GA and GP-SPSA hybrid techniques is that process modeling and optimization can be performed exclusively from the process input-output data without invoking the detailed knowledge of the process phenomenology. The GP-GA and GP-SPSA techniques have been employed for modeling and optimization of the glucose to gluconic acid bioprocess, and the optimized process operating conditions obtained thereby have been compared with those obtained using two other hybrid modeling-optimization paradigms integrating artificial neural networks (ANNs) and GA/SPSA formalisms. Finally, the overall optimized operating conditions given by the GP-GA method, when verified experimentally resulted in a significant improvement in the gluconic acid yield. The hybrid strategies presented here are generic in nature and can be employed for modeling and optimization of a wide variety of batch and continuous bioprocesses.

Artificial Intelligence↗

[Characteristic features of allogenic transfusions in elderly patients with ischemic heart disease in operations under conditions of extracorporeal circulation and using cell saver].

It was shown that in spite of using different methods of saving the autologous patient's blood, cell saver included, in elderly patients operated upon under conditions of extracorporeal circulation the frequency and volume of allogenic transfusions was higher as compared with the younger patients, in elderly women the allogenic transfusions being necessary more frequently.

Aged↗

High-throughput process development for recombinant protein purification.

Methods development in chromatographic purification processes is a complex operation and has traditionally relied on trial and error approaches. The availability of a large number of commercial media, choice of different modes of chromatography, and diverse operating conditions contribute to the challenging task of accelerating methods development. In this paper, we describe a novel microtiter-plate based screening method to identify the appropriate sequence of chromatographic steps that result in high purities of bioproducts from their respective culture broths. Protein mixtures containing the bioproduct were loaded on aliquots of different chromatographic media in microtiter plates. Serial step elution of the proteins, in concert with bioproduct-specific assays, resulted in the identification of "active fractions" containing the bioproduct. The identification of a successful chromatographic step was based on the purity of the active fractions, which were then pooled and used as starting material for screening the next chromatographic dimension. This procedure was repeated across subsequent dimensions until single band purities of the protein were obtained. The sequence of chromatographic steps and the corresponding operating conditions identified from the screen were validated under scaled-up conditions. Various modes of chromatography including hydrophobic interaction, ion exchange (cation and anion exchange) and hydrophobic charge-induction chromatography (HCIC), and different operating conditions (pH, salt concentration and type, etc.) were employed in the screen. This approach was employed to determine the sequence of chromatographic steps for the purification of recombinant alpha-amylase from its cell-free culture broth. Recommendations from the screen resulted in single-band purity of the protein under scaled-up conditions. Similar results were observed for an scFv-beta-lactamase fusion protein. The use of a miniaturized screen enables the parallel screening of a wide variety of actual bioprocess media and conditions and represents a novel paradigm approach for the high-throughput process development of recombinant proteins.

Anion Exchange Resins↗

A computer touch-screen apparatus for training visual discriminations in rats.

We describe an operant conditioning apparatus that uses computerized touch-screen technology and is designed for the versatile and highly controlled testing of rats in a potentially wide variety of behavioral paradigms. Although computer-controlled touch-screen systems have been developed for use with pigeons, monkeys, and humans, analogous technologies and methods have not yet been developed for rats. The development of a touch-screen system for rats could enhance the efficiency of behavioral research with rats, and may offer a unique tool for studying animal learning. In the first test of the utility of the apparatus, 3 Sprague-Dawley rats learned to activate the touch screen only after the touch-screen panel was made slightly movable. These animals then learned to discriminate visual stimuli presented on the computer monitor, but only after the food magazine and pellet dispenser were moved to the rear of the chamber opposite the stimulus display and response window. In a test of the utility of the modified apparatus, 6 Long-Evans rats learned to activate the touch screen and learned one of three different simple discriminations using computer-generated, visually presented stimuli. A basic method for training rats to activate the computer touch screen and for visual discrimination training is described. Results show that rats learned to activate the touch screen and discriminate visual stimuli presented on a computer monitor. Potential applications and advantages of the touch-screen-equipped rat operant conditioning chamber are discussed.

Animals↗

Influence of formulation on jet nebulisation quality of alpha 1 protease inhibitor.

As foam appears during solution constitution and nebulisation of alpha 1 protease inhibitor (alpha 1 PI), we selected in a previous work, antifoams likely to be associated with an alpha 1 PI solution to be nebulised: span 65 at a 0.025% concentration and cetyl alcohol at a 0.05% concentration associated with tyloxapol at 0.025% concentration. The purpose of this study was, on the one hand to study the influence of the formulation on nebulisation quality by relating physicochemical properties and nebulisation capacity, and on the other hand, to define the alpha 1 PI that will be retained for a clinical study. The properties of the different alpha 1 PI formulations are compared: surface tension, viscosity, time required to constitute the protein solution and pH. Nebulisation quality is evaluated under different operating conditions by measuring the droplet size, the quantity of alpha 1 PI nebulised, nebulisation time and the quantity of alpha 1 PI likely to reach the lungs which was subjected to statistical analysis. The statistical analysis of results indicates that the addition of the cetyl alcohol/tyloxapol mixture improves nebulisation effectiveness by significantly increasing the quantity of drug nebulised and therefore the quantity of alpha PI likely to reach the lungs. It is this formulation that will be retained for clinical trials. We check that the nebuliser and operating conditions influence all the parameters, that is to say the respirable fraction, the quantity nebulised and the nebulisation time. Although there is no interaction between the nebuliser and the formulation, nebulisation quality is the combined result of the formulation, the nebuliser and the operating conditions.

Antifoaming Agents↗